CN104402983A - Method for extracting glycoprotein by utilizing sea cucumber treatment blanching liquid and application thereof - Google Patents
Method for extracting glycoprotein by utilizing sea cucumber treatment blanching liquid and application thereof Download PDFInfo
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- CN104402983A CN104402983A CN201410754944.8A CN201410754944A CN104402983A CN 104402983 A CN104402983 A CN 104402983A CN 201410754944 A CN201410754944 A CN 201410754944A CN 104402983 A CN104402983 A CN 104402983A
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
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Abstract
The invention provides a method for extracting glycoprotein by utilizing a sea cucumber treatment blanching liquid and application thereof. The method for extracting the glycoprotein by utilizing the sea cucumber treatment blanching liquid comprises the following steps: (1) concentrating the sea cucumber treatment blanching liquid to obtain a concentrated liquid with the solid content of 15-45%; (2) drying the concentrated liquid to obtain a first solid powder; (3) adding the solid powder to 70-85% ethanol solution, stirring, desalting, removing saponin, and centrifuging or extraction filtering to collect a first solid insoluble substance; (4) repeatedly performing the steps (3) on the first solid insoluble substance for twice or three times to obtain a second solid insoluble substance without salt and the saponin; (5) adding the second solid insoluble substance to a 90-95% ethanol solution to stir, degreasing, extraction filtering to collect a third solid insoluble substance, and drying the third solid insoluble substance to obtain a second solid powder; (6) adding the second solid powder to purified water, heating and extracting to obtain an extract solution; (7) centrifuging the extract solution, removing sediment, filtering liquid supernatant, collecting filtrate, and drying the filtrate to obtain the glycoprotein with function of increasing white blood cells. The method for extracting the glycoprotein by utilizing the sea cucumber treatment blanching liquid is applied to preparation of medicines for increasing the white blood cells.
Description
Technical field
The present invention relates to a kind of Holothurian machining blanching solution that utilizes and extract the method with remarkable function of increasing leukocyte glycoprotein.
Background technology
After fishing for, there is the enzyme of proteolysis such as autolytic enzyme in fresh sea cucumber, being easy to skin, self-dissolving due to himself.For the ease of preserving, fresh sea cucumber will store through hot water scalding treatment post-treatment usually.But fresh sea cucumber produces a large amount of blanching solutions in the process of hot-water cure, contain a large amount of active substances in this blanching solution as selenka (imitating isolation identification journal of Shandong university (Edition) the 7th phase in 2011 of several selenka compound in stichopus japonicus processing-waste), sea cucumber suger albumen (ZL 2,011 1 0384722.8) etc.
Selenka has very strong haemolysis, cell toxicant, extracorporeal anti-tumor cell, antimycotic isoreactivity; Sea cucumber polysaccharide has immunomodulatory, anticoagulation and antithrombus formation, antitumor isoreactivity; Holothurian collagen have enrich blood, nourish blood, delay senility isoreactivity.But in the active material of sea cucumber that these are numerous, and the glycoprotein having no the extraction of favourable Holothurian machining blanching solution has the bibliographical information of remarkable leukocyte increasing quantity.
Summary of the invention
Object of the present invention provides a kind of Holothurian machining blanching solution that utilizes to extract the method with the glycoprotein activity component of remarkable function of increasing leukocyte, and finds that the sea cucumber blanching solution glycoprotein utilizing this extracting method to obtain has the activity of remarkable leukocyte increasing quantity.
The technical measures that the present invention takes are: a kind of method utilizing Holothurian machining blanching solution to extract glycoprotein, Holothurian machining blanching solution is concentrated into solid content between 15%-45% with concentrating under reduced pressure equipment by (1) to it is characterized in that it comprises the steps:, obtains concentrated solution;
(2) concentrated solution spraying dry obtains the first pressed powder;
(3) pressed powder joins mass percent is in 70-85% ethanolic soln, stirs, carries out desalination, removes saponin(e process, afterwards centrifugal or collected by suction first solid insoluble;
(4) first solid insoluble repeating steps (3) 2-3 time obtain and remove salinity completely, remove the second solid insoluble of saponin(e;
It is in 90-95% ethanolic soln that (5) second solid insolubles join mass percent, stirs, carries out skimming treatment, utilize collected by suction the 3rd solid insoluble afterwards, obtains the second pressed powder after the 3rd solid insoluble drying;
(6) second pressed powders join in pure water, and extract solution is extracted to obtain in heating;
(7) after extracting, extract solution removes precipitation through centrifugal Horizontal helical type centrifuge, disc centrifuge, tubular-bowl centrifuge successively, supernatant liquor is by the membrane filtration of 10KDa, and the filter membrane that filtered solution is 5000Da by molecular weight cut-off carries out ultrafiltration, collects trapped fluid.
(8) trapped fluid drying obtains the glycoprotein fraction with function of increasing leukocyte afterwards, and in this component, protein content is between 80-90% after measured, and sugared content is between 10-20%.
Concrete feature of the present invention also has, and Holothurian machining blanching solution refers to and utilizes the processing blanching solution produced in fresh Holothurian machining blanching process as extraction material.The concrete operation step that Holothurian machining blanching solution obtains is fresh sea cucumber after dissecting and removing intestines, puts into boiling water and boils 10-30min, pulls gained liquid after sea cucumber out.
Utilize Holothurian machining blanching solution to extract the purposes of glycoprotein, it is characterized in that obtained glycoprotein as the application of medicine preparing leukocyte increasing.
The functions and effects that glycoprotein that the present invention utilizes Holothurian machining blanching solution to extract has leukocyte increasing are further illustrated below by the pharmacodynamic experiment of animal model and clinical trial.
Pharmacodynamic experiment: be cause hypoimmunity mice white corpuscle for model with endoxan (CTX), adopts the mode of oral administration, observes the glycoprotein of the present invention's extraction to the impact of murine interleukin.
Regular grade Kunming mouse 50 is divided into 5 groups at random, these 5 groups are respectively: the glycoprotein high dose group that in the glycoprotein that the glycoprotein low dose group that model control group, sea cucumber blanching solution extract, sea cucumber blanching solution extract, dosage group, sea cucumber blanching solution extract, Recombinant Human Granulocyte Colony-stimulating Factor Injection (auspicious white) drug-positive control group, often organize 10.Wherein
Model control group: gavage gives pure water;
The glycoprotein low dose group that sea cucumber blanching solution extracts: give sea cucumber blanching solution glycoprotein aqueous solution 0.93g/kgd dosage gavage;
Dosage group in the glycoprotein that sea cucumber blanching solution extracts: give sea cucumber blanching solution glycoprotein aqueous solution 1.86g/kgd dosage gavage;
The glycoprotein low dose group that sea cucumber blanching solution extracts: give sea cucumber blanching solution glycoprotein aqueous solution 3.72g/kgd dosage gavage;
Recombinant Human Granulocyte Colony-stimulating Factor Injection (auspicious white) drug-positive control group: the auspicious white solution 50 μ g/kgd of tail vein injection.
Experimentation: manufacture immunodeficiency models, continuous ip 4 days, every day 1 time to 50 mouse peritoneal injection (ip) cyclophosphamide solution 80mg/kg.Give the glycoprotein solution of (ig) different concns sea cucumber blanching solution extraction according to body weight gavage from modeling each trial-product group on the same day, administration volume is 0.2ml/10g, the intravenous injection of drug-positive control group is auspicious white solution 50 μ g/kg (iv), administration volume is 0.2ml/10g, model control group ig isometric(al) pure water, successive administration 6 days.
After last administration, 2h plucks eyeball and gets blood, carries out routine blood test mensuration.
Experimental result: abdominal injection gave mouse endoxan (80mg/kg/d) in continuous 4 days, and after 6 days, murine interleukin is starkly lower than normal value.Compare with model control group, in the glycoprotein that sea cucumber blanching solution extracts, dosage group has leukogenic effect, and wherein the effect of 1.86g/kg/d group is remarkable, compare with model control group, difference has significance (4.94vs2.65, P<0.05), and data see the following form 1.
The glycoprotein that table 1 sea cucumber blanching solution extracts causes the leukocytic impact of hypoimmunity mice to endoxan
Note:
The glycoprotein fraction clinical experiment that the present invention extracts from sea cucumber blanching solution:
Case one: seedling, female, 59 years old, Jinzhou district.Patient with breast cancer, the rapid drawdown of Leukocytes after Chemotherapy quantity, takes shengbai drug, and long-term quantity of leucocyte is 3.1 × 10
9-3.3 × 10
9between often liter.After taking the glycoprotein of this invention extraction, one day 6g, after taking ten days, quantity of leucocyte reaches 4.2 × 10
9often liter.
Case two: Wang, man, 62 years old, Tiger Mountain town, Rongcheng City.Patients with lung cancer, the rapid drawdown of Leukocytes after Chemotherapy quantity, takes shengbai drug, and long-term quantity of leucocyte is 2.8 × 10
9-3.0 × 10
9between often liter.After taking the glycoprotein of this invention extraction, one day 6g, after taking ten days, quantity of leucocyte reaches 3.8 × 10
9often liter.
Case three: Zhang, female, 58, Xuhui District, Shanghai.Patient with breast cancer, the rapid drawdown of Leukocytes after Chemotherapy quantity, takes shengbai drug, and long-term quantity of leucocyte is 2.4 × 10
9-3.4 × 10
9between often liter.After taking the glycoprotein of this invention extraction, one day 6g, after taking ten days, quantity of leucocyte reaches 4.1 × 10
9often liter.
Clinical experiment also shows, the glycoprotein analog material utilizing the present invention to extract from Holothurian machining blanching solution has the effect of significant leukocyte increasing quantity.
The invention has the beneficial effects as follows the processing blanching solution making full use of and produce in fresh Holothurian machining process, utilize aforesaid method, the sea cucumber suger protein component with remarkable function of increasing leukocyte can be obtained.The most outstanding feature of the present invention obtains dry powder substance by concentrated, spraying dry, reduces the usage quantity of subsequent ethanol solution; The ethanolic soln utilizing mass percent to be 70-85% afterwards carries out desalination, removes saponin(e process, and the ethanolic soln utilizing again mass percent to be 90-95% carries out skimming treatment, makes the composition such as salt, saponin(e, lipid effectively removed in sea cucumber blanching solution; Utilize again membrane technique to be separated and obtain the glycoprotein analog component of molecular weight between 5000-10000Da; effectively eliminate the composition such as albumen, taurine, small peptide in sea cucumber blanching solution; the glycoprotein analog component of this molecular weight section has significant rising effect to the quantity of leucocyte reduction caused after Chemotherapy of Tumor Patients, and to quantity of leucocyte, normal patient has no effect.This technological method improves the higher value application level of Holothurian machining blanching solution greatly, and product has high health care and pharmaceutical use.
Embodiment
embodiment 1:
Utilize Holothurian machining blanching solution to extract a method for glycoprotein, it is characterized in that it comprises the steps: (1) and collect Holothurian machining blanching solution 4000L, concentrating under reduced pressure, is concentrated into volume 300L, and solid content is about 35%.
(2) concentrated solution spraying dry obtains pressed powder;
(3) powder joins in 500L 80% ethanolic soln, stirs desalination, de-saponin(e process, after stirring 24h, utilizes link-suspended basket centrifuge centrifugal, rotating speed 1850rpm, centrifugal collecting precipitation;
(4) precipitate repeating step (3) 3 times, obtain the throw out of desalination, de-saponin(e 4 times;
(5) above-mentioned throw out joins in 500L 90% ethanolic soln, stirs 24h, removes fat, utilize pumping and filtering device suction filtration, collects filter residue, obtains pressed powder after filter residue and drying;
(6) pressed powder joins in 2000L pure water, is heated to 100 DEG C and keeps 60min, rapidly latter 4 DEG C of cooling, first through Horizontal helical type centrifuge (3000rpm), again through disk plate centrifuge (rotating speed 6000rpm), finally by tubular-bowl centrifuge (rotating speed 12000rpm), collected after centrifugation supernatant liquor;
(7) supernatant liquor is by the membrane filtration of molecular weight cut-off 10KDa, and the filter membrane that filtered solution is 5000Da by molecular weight cut-off carries out ultrafiltration, collects trapped fluid;
(8) trapped fluid drying is afterwards for having the glycoprotein fraction (protein content 84% after testing, polysaccharide content 14%) of function of increasing leukocyte.
embodiment 2:
Utilize Holothurian machining blanching solution to extract a method for glycoprotein, it is characterized in that it comprises the steps: (1) and collect Holothurian machining blanching solution 4000L, concentrating under reduced pressure, is concentrated into volume 300L, and solid content is about 35%.
(2) concentrated solution spraying dry obtains pressed powder;
(3) powder joins in 500L 75% ethanolic soln, stirs desalination, de-saponin(e process, after stirring 24h, utilizes pumping and filtering device suction filtration, collect filter residue;
(4) filter residue joins in 500L 75% ethanolic soln, repeating step (3) 3 times, obtains the filter residue of desalination, de-saponin(e 4 times;
(5) above-mentioned filter residue joins in 500L 95% ethanolic soln, stirs 24h, removes fat, utilize pumping and filtering device suction filtration, collects filter residue, obtains pressed powder after filter residue and drying;
(6) pressed powder joins in 2000L pure water, is heated to 100 DEG C and keeps 60min, rapidly latter 4 DEG C of cooling, first through Horizontal helical type centrifuge (3000rpm), again through disk plate centrifuge (rotating speed 6000rpm), finally by tubular-bowl centrifuge (rotating speed 12000rpm), collected after centrifugation supernatant liquor;
(7) supernatant liquor is by the membrane filtration of molecular weight cut-off 10KDa, and the filter membrane that filtered solution is 5000Da by molecular weight cut-off carries out ultrafiltration, collects trapped fluid;
(8) trapped fluid drying is afterwards for having the glycoprotein fraction (protein content 83% after testing, polysaccharide content 15%) of function of increasing leukocyte.
Embodiment 3: the present embodiment and embodiment 1 something in common repeat no more, difference is that a kind of purposes utilizing Holothurian machining blanching solution to extract glycoprotein is the application as the medicine preparing leukocyte increasing.
Claims (3)
1. utilize Holothurian machining blanching solution to extract the method for glycoprotein, Holothurian machining blanching solution is concentrated into solid content between 15%-45% with concentrating under reduced pressure equipment by (1) to it is characterized in that it comprises the steps:, obtains concentrated solution;
(2) concentrated solution spraying dry obtains the first pressed powder;
It is in 70-85% ethanolic soln that (3) first pressed powders join mass percent, stirs, carries out desalination, removes saponin(e process, afterwards centrifugal or collected by suction first solid insoluble;
(4) first solid insoluble repeating steps (3) 2-3 time obtain and remove salinity completely, remove the second solid insoluble of saponin(e;
It is in 90-95% ethanolic soln that (5) second solid insolubles join mass percent, stirs, carries out skimming treatment, utilize collected by suction the 3rd solid insoluble afterwards, obtains the second pressed powder after the 3rd solid insoluble drying;
(6) second pressed powders join in pure water, and extract solution is extracted to obtain in heating;
(7) after extracting, extract solution removes precipitation through centrifugal Horizontal helical type centrifuge, disc centrifuge, tubular-bowl centrifuge successively, supernatant liquor is by the membrane filtration of 10KDa, and the filter membrane that filtered solution is 5000Da by molecular weight cut-off carries out ultrafiltration, collects trapped fluid;
(8) trapped fluid drying obtains the glycoprotein fraction with function of increasing leukocyte afterwards.
2. the method utilizing Holothurian machining blanching solution to extract glycoprotein according to claim 1, is characterized in that Holothurian machining blanching solution refers to and utilizes the processing blanching solution produced in fresh Holothurian machining blanching process as extraction material.
3. the Holothurian machining blanching solution that utilizes according to claim 1 extracts the purposes of glycoprotein, it is characterized in that obtained glycoprotein as the application of medicine preparing leukocyte increasing.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105266075A (en) * | 2015-10-24 | 2016-01-27 | 山东好当家海洋发展股份有限公司 | Method for extracting holothurian saponins by using holothurian blanching liquid |
| CN111411014A (en) * | 2020-03-25 | 2020-07-14 | 宁波宝新不锈钢有限公司 | Harmless treatment method for stainless steel rolling oil sludge |
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| CN101585873A (en) * | 2009-07-09 | 2009-11-25 | 大连水产学院 | From waste sea cucumber processing liquid, reclaim the method for protein and Crude polysaccharides |
| CN102406048A (en) * | 2011-11-29 | 2012-04-11 | 山东好当家海洋发展股份有限公司 | Method for preparing sea cucumber glycoprotein by using sea cucumber blanching solution |
| CN103951759A (en) * | 2014-04-22 | 2014-07-30 | 钦州市山海生物科技有限公司 | Method for extracting sea cucumber polysaccharide from sea cucumber |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101343332A (en) * | 2008-08-20 | 2009-01-14 | 山东省科学院生物研究所 | Method for extracting holothurian polyoses with holothurian processing waste liquor |
| CN101585873A (en) * | 2009-07-09 | 2009-11-25 | 大连水产学院 | From waste sea cucumber processing liquid, reclaim the method for protein and Crude polysaccharides |
| CN102406048A (en) * | 2011-11-29 | 2012-04-11 | 山东好当家海洋发展股份有限公司 | Method for preparing sea cucumber glycoprotein by using sea cucumber blanching solution |
| CN103951759A (en) * | 2014-04-22 | 2014-07-30 | 钦州市山海生物科技有限公司 | Method for extracting sea cucumber polysaccharide from sea cucumber |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105266075A (en) * | 2015-10-24 | 2016-01-27 | 山东好当家海洋发展股份有限公司 | Method for extracting holothurian saponins by using holothurian blanching liquid |
| CN105266075B (en) * | 2015-10-24 | 2020-01-31 | 山东好当家海洋发展股份有限公司 | method for extracting Stichopus japonicus saponins from Stichopus japonicus blanching liquid |
| CN111411014A (en) * | 2020-03-25 | 2020-07-14 | 宁波宝新不锈钢有限公司 | Harmless treatment method for stainless steel rolling oil sludge |
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